This project addresses three separate issues related to the kinetics of HbS polymerization and the formation of domains. The three principle issues are: (1) the effect of components of the red cell on homogenous nucleation; (2) the effect of domain formation on mass distribution of both polymerized and free HbS in the gelled sample and (3) the effects of the subunit tertiary structure on the thermodynamics and kinetics of polymerization. Ferrone lists three specific aims in this project A.)Measurements of the homogenous nucleation rates of HbS in the presence of membrane preparations including inside-out vesicles of Hb A and Hb S cells with and without spectrin. Any preparation in which effects are observed in the initial observations will be subjected to detailed studies. B.) Polymer domain formation will be studied in a series of hemoglobins prepared by site directed mutagenesis. C) Double mutant models for partially liganded hemoglobins (e.g. Hb S/M Hyde Park or partially saturated NOHbS) will be characterized kinetically and thermodynamically in dilute and in concentrated solutions.